The Evolving Role of the Rheumatology Practitioner in the Care of Immunocompromised Patients in the <scp>COVID</scp>‐19 Era
Authors: Leonard H. Calabrese, Cassandra M. Calabrese, Elizabeth Kirchner, Kevin Winthrop
Journal: Arthritis & Rheumatology (2022)

The impact of the global COVID-19 pandemic on the field of rheumatology has been dramatic and broad-ranging. These effects include the pandemic's ongoing influence on models of care delivery, the intermittent impact on drug availability to our patients, and the output of research our field has contributed to increasing our understanding of the disease's epidemiology, basic and clinical immunology, clinical outcomes, and vaccinology in immunocompromised hosts. The next phase of the pandemic cannot be totally predicted, but there is broad agreement that SARS–CoV-2 as a global pathogen is unlikely to disappear quietly; the virus appears to be becoming endemic, and it is likely we will face continued emerging variants of unpredictable pathogenicity. If this prediction comes to fruition, SARS–CoV-2 infections will likely impact the population along 2 different paths. The first and most common scenario will be new or recurrent infection among healthy, previously exposed, or vaccinated individuals whose disease course will, in the vast majority of cases, be of lesser severity and low mortality. The second more troubling scenario will occur with infections in our immunocompromised patients who, even if vaccinated, are more likely to experience severe outcomes from the disease (1, 2). We, as rheumatologists, must prepare for the latter scenario even though it is yet to be determined what will constitute best practice models for both prevention and care for our immunocompromised patients. There is clearly no one-size-fits-all approach, as rheumatologists practice in many different models of care, ranging from solo practices to small- and large-group practices, multispecialty, and hospital-based practices; in each of these settings, practitioners have access to varying levels of resources. The goals, however, are the same for all of us: protecting our most vulnerable patients from infection wherever possible and contributing to providing or directing those who become infected to the best possible care. While these goals seem unassailable, they raise important questions about the boundaries of rheumatologic care. These questions are similar, in some ways, to the controversies surrounding our role in the care of other non-rheumatologic problems: cardiovascular risk management, diagnosis and treatment of infections, providing vaccinations, and management of other medical problems in patients with complex conditions. One could easily ask whether COVID-19 should be considered different from any other medical problem we may either treat ourselves or refer to others. We believe it is different, and accordingly, we would like to start a discussion within the rheumatology profession in this call to action by posing a series of questions and possible answers regarding how these goals may be achieved. Defining and determining precisely who is immunocompromised is surprisingly difficult and a work continually in progress. Definitions put forth by the Centers for Disease Control and Prevention (CDC) (3) are inadequate and note that such determination may be best arrived at in consultation with a specialist. Data from numerus studies including the COVID-19 Global Rheumatology Alliance (4) and others (5) have provided insights into epidemiologic factors imparting risk, including comorbidities, disease activity, and the use of certain immunomodulatory drugs, especially rituximab and glucocorticoids. While the utility of measuring serologic response to vaccine has also been discouraged by the CDC (6) and is not currently recommended by the American College of Rheumatology (ACR) COVID-19 Vaccine Task Force due to lack of supportive data at the time of last guidance release, other groups such as the transplantation community (7) have advocated for such testing to identify the most vulnerable among their patients. The status quo of such a nonspecific definition is not acceptable, and we urgently need to develop more quantitative biomarkers, both clinical and laboratory-based, to identify those among our community who are most at risk and need prioritization of resources. While prevention of infection is clearly the most desirable strategy for limiting the effects of COVID-19 on our immunocompromised patients, our capacity to achieve this with continued viral evolutionary escape has become challenging, and we have more realistically moved to preventing severe outcomes, including death from primary or breakthrough infection, as our highest priority. The most powerful preventive measure currently available against severe clinical outcomes is vaccination; however, both patients and practitioners are often confused by the rapidly changing guidelines for immunocompromised individuals, as well as the general community, and thus need to be continually educated. Despite strong evidence of benefit from vaccination, additional dosing, and boosting, it is unfortunate that not all of our patients are willing or able to be vaccinated (8). Furthermore, and implicit in the definition of the immunocompromised state, those most heavily immunocompromised are unlikely to fully respond, both immunologically and clinically, to vaccinations; this includes those receiving rituximab as well as other immunosuppressive therapies (2, 9). Providing clear education to our most immunocompromised patients regarding the continued use of some level of nonpharmacologic measures of infection, including masking in public and social distancing when appropriate, is also important (10). Most important for the most severely immunocompromised patients, however, is preexposure prophylaxis with tixagevimab and cilgavimab, which have been demonstrated to significantly reduce the likelihood and severity of COVID-19 (11). Often unclear is exactly who on the health care team should initiate such discussions and referrals, which may lead to lapses in administration to those who would benefit most. Consideration of individual practices and groups should be given to system-based screening of patient treatment records to identify those at the highest risk, such as those undergoing B cell–depletion therapy, and proactively contact those patients to ensure that preexposure prophylaxis has been offered and encouraged. It is our belief that the rheumatologist should take the lead in preexposure prophylaxis and accordingly must commit to both learning about the therapy and becoming familiar with how and where it can be accessed in their area. Rheumatologists in general will have a limited role in managing patients hospitalized with COVID-19, but they will be confronted with determining what their role is in diagnosing and managing outpatients. The armamentarium of COVID-19 outpatient treatments is rapidly growing (12) and includes monoclonal antibodies (a constantly changing option due to viral escape), which need to be administered within a specific timeline (generally 7–10 days) (13), as well as both a single parenteral and several oral antiviral agents, which must also be given within a critical time window (i.e., 0–5 days after symptom onset for oral therapies, 0–7 days for parenteral therapy) (12). With this in mind, we believe that rheumatology practitioners must educate our immunocompromised patients on how to be rapidly diagnosed and treated, in the event that they do become infected (Figure 1). Such education includes an understanding of the time urgency of available therapies, vigilance for early signs or symptoms of COVID-19, and encouraging access to rapid testing (preferably at home). Another critical step in optimal COVID-19 outpatient care is clear awareness of who to call once an immunocompromised patient is diagnosed or strongly suspected of having COVID-19; such a resource (i.e., physician, advanced practitioner, consultant) can then direct the patient to the appropriate outpatient treatment without delay. Each practice setting, whether solo, small- or large-group, or academic center should have its own network of consultants to refer patients to or commit to take it upon themselves to initiate such therapies. Finally, it is unknown whether our immunocompromised patients will have more severe or more frequent sequelae from COVID-19 (post-acute sequelae of COVID-19, or long COVID), but early research demonstrates that prolonged symptom duration is common in our patients (14). Given the current lack of firm diagnostic criteria or biomarkers and no evidence-based therapies, the profession will have to remain engaged in active research to answer these questions; our future role in diagnosis and management for now is far from clear. Defining our role in this rapidly changing landscape of care will continue to be challenging, and we propose that, at minimum, rheumatologists should maintain declarative knowledge of COVID-19, allowing them to educate their immunocompromised patients, critically appraise the data on preventative and therapeutic options, and be able to prescribe or at least direct immunocompromised patients to the most current and effective care pathway in the event of infection. Given the explosion of peer-reviewed publications, pre–peer review publications, and online sources of unfiltered data often referred to as gray literature (e.g., as of July 1, 2022, there are >11 billion citations on COVID-19), it is more challenging than ever to be confident in our knowledge base regarding the changing practice standards for COVID-19 prevention and management. As a result, most practitioners must rely on real-time or living guidelines on disease management from organizations invested in providing such guidance. Examples of such information include the National Institutes of Health, CDC, Infectious Disease Society of America, and the ongoing efforts by the ACR (15), which summarize and provide the best available evidence, including vaccine recommendations, nonpharmacologic and pharmacologic preventive measures, and outpatient therapeutic options. Rheumatology meetings and educational venues must also step in to address clinical needs surrounding prevention and management for the practitioner in addition to presenting the latest basic and clinical science on the disease. The road ahead unfortunately appears to be a long one, and we as professionals who manage immunocompromised patients have an additional formidable challenge to address through education, prevention, and management (12). All authors drafted the article, revised it critically for important intellectual content, and approved the final version to be published. Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.